It has been disclosed in the literature that compounds which are suitable as inhibitors of HSL can be employed for the treatment of diabetes mellitus. Thus, benzotriazole derivatives are employed for this purpose in WO 2004/035550. In WO 03/105860 derivatives of boric acid and boric esters, and in WO 03/051842 inter alia amides having a hydrolyzable group, are used as HSL inhibitors. However, the suitability of aminomethylenesulfonamides as HSL inhibitors has not previously been described.
sulfonamide compounds have been disclosed in the literature, which, however, differ from those of the present invention through a different substitution pattern and having different uses (indications).
R. Neidlein et al., Monatshefte für Chemie 116 (1985), pages 651 to 660 describe syntheses and spectroscopic properties of alkylmercaptoalkylaminomethylenesulfonamides. These compounds obligatorily have two aminomethylenesulfonamide substituents in meta position on the benzene fragment, whereas the compounds of the invention have only one such substituent. No connection is made between the compounds described in R. Neidlein et al. and any use as medicaments.
U.S. Pat. No. 3,009,910 describes 2,4-disulfamylanilline derivatives and their use as medicaments with diuretic action. Whereas the methylenesulfonamide substituent is in the position ortho to R1 (for example halogen) and in the position para to R2 (for example —NH2) in the compounds of the invention, this substitution pattern is exactly reversed in the compounds disclosed in U.S. Pat. No. 3,009,910. The methylenesulfonamide substituent is located on the central benzene fragment in the position ortho to an amino substituent and in the position para to a halogen substituent. However, no connection between the compounds described in U.S. Pat. No. 3,009,910 with the treatment of diabetes, or the use of these compounds as inhibitor of HSL, is disclosed in this document.
EP-A 0 008 433 relates to sulfamoylbenzene derivatives and to their use as diuretics and saluretics. The compounds described therein differ from the sulfonamides of the invention to the extent that the central benzene fragment has an unsubstituted sulfamoyl substituent in the position ortho to a halogen substituent. Several routes are indicated for the synthesis of the compounds described in EP-A 0 008 433, the starting materials employed being inter alia the following of the formulae A and B;

The radicals R1 to R4 in the compounds of the formula A are defined independently of one another as hydrogen or an alkyl radical having 1 to 4 carbon atoms, it being possible for one of the radicals R1 to R4 also to be a carboxyl, hydroxymethyl or an alkyloxycarbonyl group having a maximum of 5 carbon atoms or for one or two of the radicals R1 to R4 to be isopropyl, isobutyl, tert-butyl, phenyl or cycloalkyl having 5 to 6 carbon atoms, X is defined as halogen, Z is defined as leaving group (halogen, hydroxy, trialkylammonium, mesylate or tosylate) and B is defined either as 2 hydrogen atoms or a protective group of the formula ═CR5—NR6R7, where the radicals R5 to R7 may independently of one another be an alkyl group having 1 to 4 carbon atoms and R5 may optionally also be hydrogen. The compounds of the formulae A and B can in each case also be rearranged to intermediate compounds in which the substituent located in the position para to the halogen substituent is defined as —C(O)—O—CR3R4—CR1R2—NH2. The aforementioned intermediate compounds which are disclosed as such in EP-A 0 008 433 and for which no use as medicament is described are not an aspect of the present invention.
DE-A 25 18 999 relates to further sulfamylbenzoic acid derivatives which can likewise be used as diuretics or saluretics. Corresponding to EP-A 0 008 433, the pharmaceutically active compounds of the general formula I described in DE-A 25 18 999 also differ through the substitution pattern on the central benzene fragment, which has an amino substituent in the position ortho to a halogen substituent, while the compounds of the invention are unsubstituted at this position. The compounds described in DE-A 25 18 999 are prepared starting from sulfamylbenzoic acid derivatives of a general formula III which have a (—COOR) substituent, where R is hydrogen, an alkyl or cycloalkyl radical having up to 6 carbon atoms, on the central benzene fragment in the position para to the halogen substituent Y. These aforementioned intermediate compounds of the general formula III of DE-A 25 18 999, which are disclosed as such therein and for which no use as medicaments is described, are not an aspect of the present invention.
EP-A 0 324 988 and EP-A 0 324 184 describe further medicinal products with diuretic and saluretic effect, of (in each case) a general formula I, which have an unsubstituted sulfamyl substituent in the position ortho to the chlorine substituent of the central benzene fragment. In addition, the compounds of the formula I in EP-A 0 324 988 have an amide substituent, which is substituted in turn by unsubstituted or at least monosubstituted benzimidazolyl, in the position para to the chlorine substituent; the amide substituent in EP-A 0 324 184 is substituted by unsubstituted or at least monosubstituted (1,2,3,4-tetrahydroisoquinolinyl). In analogy to EP-A 0 008 433, the active pharmaceutical ingredients mentioned in the two aforementioned EP applications are synthesized from precursors which have a dialkylaminomethylenesulfamyl substituent instead of an unsubstituted sulfamyl substituent. The intermediate compounds described in EP-A 0 324 988 and EP-A 0 324 184, which are disclosed as such and for which no use as medicament is described, are not an aspect of the present invention.